X-LINKED DOMINANT CHARCOT-MARIE-TOOTH-DISEASE - NERVE BIOPSIES ALLOW MORPHOLOGICAL EVALUATION AND DETECTION OF CONNEXIN32 MUTATIONS (ARG15TRP, ARG22GLN)

X-linked Charcot-Marie-Tooth neuropathy (CMTX) is caused by mutations in the connexin32 gene on Xq13. Because of overlapping morphological a nd clinical data, CMTX patients often meet the criteria of autosomal-d ominant CMT2, the neuronal type of CMT. Hence, it might be useful to a nalyse the connexin32 gene in suspected CMT2 patients when there is no male-to-male transmission. We selected a cohort of 30 patients who we re considered having CMT2 on the basis of previous clinical and histop athological evaluation. DNA was extracted from paraffin-embedded sural nerve biopsy samples and screened for connexin32 mutations to verify the possible diagnosis of CMTX. In 2 patients mutations were found cor responding to amino acid substitutions of arginine for tryptophan in c odon 15 and arginine for glutamine in codon 22 of connexin32. This stu dy illustrates that archival material allows genetic classification of suspected CMT cases. Furthermore, there is additional proof that conn exin32 mutations represent the underlying genetic defect in some cases of predominantly neuronal CMT.